Inhibition of Testicular Steroidogenesis by the Xenoestrogen Bisphenol A Is Associated with Reduced Pituitary Luteinizing Hormone Secretion and Decreased Steroidogenic Enzyme Gene Expression in Rat Leydig Cells
Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 μg/kg·d (a dose that approximates BPA levels in the environment) from postnatal d 21–35 suppressed ser...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2004-02, Vol.145 (2), p.592-603 |
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| creator | Akingbemi, Benson T Sottas, Chantal M Koulova, Anna I Klinefelter, Gary R Hardy, Matthew P |
| description | Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 μg/kg·d (a dose that approximates BPA levels in the environment) from postnatal d 21–35 suppressed serum LH (0.21 ± 0.05 ng/ml; vs. control, 0.52 ± 0.04; P < 0.01) and testosterone (T) levels (1.62 ± 0.16 ng/ml; vs. control, 2.52 ± 0.21; P < 0.05), in association with decreased LHβ and increased estrogen receptor β pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nm BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17α-hydroxylase/17–20 lyase. BPA decreased serum 17β-estradiol levels from 0.31 ± 0.02 ng/ml (control) to 0.22 ± 0.02, 0.19 ± 0.02, and 0.23 ± 0.03 ng/ml in rats exposed to 2.4 μg, 10 μg, or 100 mg/kg·d BPA, respectively, from 21–35 d of age (P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 ± 34 (control) to 261 ± 22 (P < 0.05) ng/ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility. |
| doi_str_mv | 10.1210/en.2003-1174 |
| format | Article |
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In this report exposure of rats to 2.4 μg/kg·d (a dose that approximates BPA levels in the environment) from postnatal d 21–35 suppressed serum LH (0.21 ± 0.05 ng/ml; vs. control, 0.52 ± 0.04; P < 0.01) and testosterone (T) levels (1.62 ± 0.16 ng/ml; vs. control, 2.52 ± 0.21; P < 0.05), in association with decreased LHβ and increased estrogen receptor β pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nm BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17α-hydroxylase/17–20 lyase. BPA decreased serum 17β-estradiol levels from 0.31 ± 0.02 ng/ml (control) to 0.22 ± 0.02, 0.19 ± 0.02, and 0.23 ± 0.03 ng/ml in rats exposed to 2.4 μg, 10 μg, or 100 mg/kg·d BPA, respectively, from 21–35 d of age (P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 ± 34 (control) to 261 ± 22 (P < 0.05) ng/ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2003-1174</identifier><identifier>PMID: 14605012</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>17β-Estradiol ; Aging ; Androgens - biosynthesis ; Animals ; Animals, Newborn - growth & development ; Aromatase ; Aromatase - genetics ; Aromatase - metabolism ; Benzhydryl Compounds ; Biological and medical sciences ; Biosynthesis ; Bisphenol A ; Dentistry ; Dose-Response Relationship, Drug ; Enzymes ; Estradiol - blood ; Estrogen Receptor beta ; Estrogen receptors ; Estrogens ; Estrogens, Non-Steroidal - pharmacology ; Exposure ; Female ; Fertility ; Food packaging ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression - drug effects ; Human populations ; Leydig cells ; Leydig Cells - drug effects ; Leydig Cells - enzymology ; Luteinizing hormone ; Luteinizing Hormone - blood ; Luteinizing Hormone - secretion ; Luteinizing Hormone, beta Subunit - genetics ; Male ; Organ Size - drug effects ; Perinatal exposure ; Phenols - pharmacology ; Pituitary ; Pituitary Gland - drug effects ; Pituitary Gland - secretion ; Polycarbonate ; Population studies ; Postpartum period ; Pregnancy ; Rats ; Rats, Long-Evans ; Receptors, Estrogen - genetics ; Resins ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Seminal Vesicles - growth & development ; Sex hormones ; Steroidogenesis ; Steroids - biosynthesis ; Testes ; Testis - embryology ; Testis - growth & development ; Testosterone ; Testosterone - biosynthesis ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2004-02, Vol.145 (2), p.592-603</ispartof><rights>Copyright © 2004 by The Endocrine Society 2004</rights><rights>2004 INIST-CNRS</rights><rights>Copyright © 2004 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-e55bcd76f8d8542bb2ca99bcef6132f9443c39bfcb35a32d155a9ff4046b0e7f3</citedby><cites>FETCH-LOGICAL-c459t-e55bcd76f8d8542bb2ca99bcef6132f9443c39bfcb35a32d155a9ff4046b0e7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15419698$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14605012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akingbemi, Benson T</creatorcontrib><creatorcontrib>Sottas, Chantal M</creatorcontrib><creatorcontrib>Koulova, Anna I</creatorcontrib><creatorcontrib>Klinefelter, Gary R</creatorcontrib><creatorcontrib>Hardy, Matthew P</creatorcontrib><title>Inhibition of Testicular Steroidogenesis by the Xenoestrogen Bisphenol A Is Associated with Reduced Pituitary Luteinizing Hormone Secretion and Decreased Steroidogenic Enzyme Gene Expression in Rat Leydig Cells</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 μg/kg·d (a dose that approximates BPA levels in the environment) from postnatal d 21–35 suppressed serum LH (0.21 ± 0.05 ng/ml; vs. control, 0.52 ± 0.04; P < 0.01) and testosterone (T) levels (1.62 ± 0.16 ng/ml; vs. control, 2.52 ± 0.21; P < 0.05), in association with decreased LHβ and increased estrogen receptor β pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nm BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17α-hydroxylase/17–20 lyase. BPA decreased serum 17β-estradiol levels from 0.31 ± 0.02 ng/ml (control) to 0.22 ± 0.02, 0.19 ± 0.02, and 0.23 ± 0.03 ng/ml in rats exposed to 2.4 μg, 10 μg, or 100 mg/kg·d BPA, respectively, from 21–35 d of age (P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 ± 34 (control) to 261 ± 22 (P < 0.05) ng/ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility.</description><subject>17β-Estradiol</subject><subject>Aging</subject><subject>Androgens - biosynthesis</subject><subject>Animals</subject><subject>Animals, Newborn - growth & development</subject><subject>Aromatase</subject><subject>Aromatase - genetics</subject><subject>Aromatase - metabolism</subject><subject>Benzhydryl Compounds</subject><subject>Biological and medical sciences</subject><subject>Biosynthesis</subject><subject>Bisphenol A</subject><subject>Dentistry</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzymes</subject><subject>Estradiol - blood</subject><subject>Estrogen Receptor beta</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Estrogens, Non-Steroidal - pharmacology</subject><subject>Exposure</subject><subject>Female</subject><subject>Fertility</subject><subject>Food packaging</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Human populations</subject><subject>Leydig cells</subject><subject>Leydig Cells - drug effects</subject><subject>Leydig Cells - enzymology</subject><subject>Luteinizing hormone</subject><subject>Luteinizing Hormone - blood</subject><subject>Luteinizing Hormone - secretion</subject><subject>Luteinizing Hormone, beta Subunit - genetics</subject><subject>Male</subject><subject>Organ Size - drug effects</subject><subject>Perinatal exposure</subject><subject>Phenols - pharmacology</subject><subject>Pituitary</subject><subject>Pituitary Gland - drug effects</subject><subject>Pituitary Gland - secretion</subject><subject>Polycarbonate</subject><subject>Population studies</subject><subject>Postpartum period</subject><subject>Pregnancy</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Receptors, Estrogen - genetics</subject><subject>Resins</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Seminal Vesicles - growth & development</subject><subject>Sex hormones</subject><subject>Steroidogenesis</subject><subject>Steroids - biosynthesis</subject><subject>Testes</subject><subject>Testis - embryology</subject><subject>Testis - growth & development</subject><subject>Testosterone</subject><subject>Testosterone - biosynthesis</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUFvEzEQhVcIREvhxhmNhIALW-y1nd09hhDaSJFAbZG4rbzeceJqY6e2V5D-TH4R3iZSEIKT9UbfzDzPy7KXlJzTgpIPaM8LQlhOackfZae05iIvaUkeZ6eEUJaXRVGeZM9CuE2Sc86eZieUT4ggtDjNfi3s2rQmGmfBabjBEI0aeunhOqJ3pnMrtBhMgHYHcY3wHa1LkB_r8NGE7ToVepjCIsA0BKeMjNjBDxPXcIXdoJL4auJgovQ7WA4RjTX3xq7g0vmNswjXqDw-GJC2g0-jkiF1_WHAKJjb-90G4SK5gfnPrccQxhZj4UpGWOKuMyuYYd-H59kTLfuALw7vWfbt8_xmdpkvv1wsZtNlrrioY45CtKorJ7rqKsGLti2UrOtWoZ5QVug6XUqxutWqZUKyoqNCyFprTvikJVhqdpa93c_denc3pJs0GxNUciAtuiE0FaGkYlQk8PVf4K0bvE3eGkYZEaxgFUnU-z2lvAvBo2623mzS0RpKmjHpBm0zJt2MSSf81WHo0G6wO8KHaBPw5gDIoGSvvbTKhCMnOK0ndZW4d3vODdv_rcwPK9meRNs55Y3FhxiOv_mn0d_K0NJt</recordid><startdate>20040201</startdate><enddate>20040201</enddate><creator>Akingbemi, Benson T</creator><creator>Sottas, Chantal M</creator><creator>Koulova, Anna I</creator><creator>Klinefelter, Gary R</creator><creator>Hardy, Matthew P</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20040201</creationdate><title>Inhibition of Testicular Steroidogenesis by the Xenoestrogen Bisphenol A Is Associated with Reduced Pituitary Luteinizing Hormone Secretion and Decreased Steroidogenic Enzyme Gene Expression in Rat Leydig Cells</title><author>Akingbemi, Benson T ; Sottas, Chantal M ; Koulova, Anna I ; Klinefelter, Gary R ; Hardy, Matthew P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-e55bcd76f8d8542bb2ca99bcef6132f9443c39bfcb35a32d155a9ff4046b0e7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>17β-Estradiol</topic><topic>Aging</topic><topic>Androgens - biosynthesis</topic><topic>Animals</topic><topic>Animals, Newborn - growth & development</topic><topic>Aromatase</topic><topic>Aromatase - genetics</topic><topic>Aromatase - metabolism</topic><topic>Benzhydryl Compounds</topic><topic>Biological and medical sciences</topic><topic>Biosynthesis</topic><topic>Bisphenol A</topic><topic>Dentistry</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzymes</topic><topic>Estradiol - blood</topic><topic>Estrogen Receptor beta</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Estrogens, Non-Steroidal - pharmacology</topic><topic>Exposure</topic><topic>Female</topic><topic>Fertility</topic><topic>Food packaging</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Human populations</topic><topic>Leydig cells</topic><topic>Leydig Cells - drug effects</topic><topic>Leydig Cells - enzymology</topic><topic>Luteinizing hormone</topic><topic>Luteinizing Hormone - blood</topic><topic>Luteinizing Hormone - secretion</topic><topic>Luteinizing Hormone, beta Subunit - genetics</topic><topic>Male</topic><topic>Organ Size - drug effects</topic><topic>Perinatal exposure</topic><topic>Phenols - pharmacology</topic><topic>Pituitary</topic><topic>Pituitary Gland - drug effects</topic><topic>Pituitary Gland - secretion</topic><topic>Polycarbonate</topic><topic>Population studies</topic><topic>Postpartum period</topic><topic>Pregnancy</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Receptors, Estrogen - genetics</topic><topic>Resins</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Seminal Vesicles - growth & development</topic><topic>Sex hormones</topic><topic>Steroidogenesis</topic><topic>Steroids - biosynthesis</topic><topic>Testes</topic><topic>Testis - embryology</topic><topic>Testis - growth & development</topic><topic>Testosterone</topic><topic>Testosterone - biosynthesis</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akingbemi, Benson T</creatorcontrib><creatorcontrib>Sottas, Chantal M</creatorcontrib><creatorcontrib>Koulova, Anna I</creatorcontrib><creatorcontrib>Klinefelter, Gary R</creatorcontrib><creatorcontrib>Hardy, Matthew P</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akingbemi, Benson T</au><au>Sottas, Chantal M</au><au>Koulova, Anna I</au><au>Klinefelter, Gary R</au><au>Hardy, Matthew P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Testicular Steroidogenesis by the Xenoestrogen Bisphenol A Is Associated with Reduced Pituitary Luteinizing Hormone Secretion and Decreased Steroidogenic Enzyme Gene Expression in Rat Leydig Cells</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2004-02-01</date><risdate>2004</risdate><volume>145</volume><issue>2</issue><spage>592</spage><epage>603</epage><pages>592-603</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 μg/kg·d (a dose that approximates BPA levels in the environment) from postnatal d 21–35 suppressed serum LH (0.21 ± 0.05 ng/ml; vs. control, 0.52 ± 0.04; P < 0.01) and testosterone (T) levels (1.62 ± 0.16 ng/ml; vs. control, 2.52 ± 0.21; P < 0.05), in association with decreased LHβ and increased estrogen receptor β pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nm BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17α-hydroxylase/17–20 lyase. BPA decreased serum 17β-estradiol levels from 0.31 ± 0.02 ng/ml (control) to 0.22 ± 0.02, 0.19 ± 0.02, and 0.23 ± 0.03 ng/ml in rats exposed to 2.4 μg, 10 μg, or 100 mg/kg·d BPA, respectively, from 21–35 d of age (P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 ± 34 (control) to 261 ± 22 (P < 0.05) ng/ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>14605012</pmid><doi>10.1210/en.2003-1174</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | 17β-Estradiol Aging Androgens - biosynthesis Animals Animals, Newborn - growth & development Aromatase Aromatase - genetics Aromatase - metabolism Benzhydryl Compounds Biological and medical sciences Biosynthesis Bisphenol A Dentistry Dose-Response Relationship, Drug Enzymes Estradiol - blood Estrogen Receptor beta Estrogen receptors Estrogens Estrogens, Non-Steroidal - pharmacology Exposure Female Fertility Food packaging Fundamental and applied biological sciences. Psychology Gene expression Gene Expression - drug effects Human populations Leydig cells Leydig Cells - drug effects Leydig Cells - enzymology Luteinizing hormone Luteinizing Hormone - blood Luteinizing Hormone - secretion Luteinizing Hormone, beta Subunit - genetics Male Organ Size - drug effects Perinatal exposure Phenols - pharmacology Pituitary Pituitary Gland - drug effects Pituitary Gland - secretion Polycarbonate Population studies Postpartum period Pregnancy Rats Rats, Long-Evans Receptors, Estrogen - genetics Resins Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Seminal Vesicles - growth & development Sex hormones Steroidogenesis Steroids - biosynthesis Testes Testis - embryology Testis - growth & development Testosterone Testosterone - biosynthesis Vertebrates: endocrinology |
| title | Inhibition of Testicular Steroidogenesis by the Xenoestrogen Bisphenol A Is Associated with Reduced Pituitary Luteinizing Hormone Secretion and Decreased Steroidogenic Enzyme Gene Expression in Rat Leydig Cells |
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